Exogenous exposure to TGF-β1 was sufficient to drive the metastasis of an otherwise in situ model of BC and was similarly associated with a depletion and return of E-cad expression during metastatic progression.
Variants in CDH1 have been linked to familial hereditary diffuse gastric cancer and invasive lobular breast cancer; however, no cases of gastric or breast cancer have been reported in our BCDS cases.
We found that increased methylation in the E-cadherin promoter region and decreased methylation in satellite 2 DNA were often present in the same breast cancers.
This study aimed to investigate the frequency of germline CDH1 mutations in patients with LBC with early onset disease or family histories of breast cancer without DGC.
To determine if CDH1 is a susceptibility gene for lobular breast cancer in women without a family history of diffuse gastric cancer, germline DNA was analysed for the presence of CDH1 mutations in 318 women with lobular breast cancer who were diagnosed before the age of 45 years or had a family history of breast cancer and were not known, or known not, to be carriers of germline mutations in BRCA1 or BRCA2.
The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir.
Although none of these associations retained statistical significance after correcting for the total number of polymorphisms evaluated, this study suggests that genetic variation in CDH1 may be associated with breast cancer risk, and that this relationship may vary by menopausal status.
E-, N-, P-, VE-, Proto-, desmosomal and FAT cadherins have been found to regulate breast cancer in positive as well as negative fashion, whereby both Ecadherin (CDH1) and N-cadherin (CDH2) contribute significantly towards transitioning from epithelial state to mesenchymal state (EMT) and enacting the abnormal cells to invade and metastasize nearby and distant tissues.
Besides, methylation status in promoter of breast cancer related genes CDH1, SFN, TNFRSF10C were also changed, which implied that BPS might play a role in the development of breast cancer.
We showed previously that breast cancer chemoprevention with benzyl isothiocyanate (BITC) in MMTV-neu mice was associated with induction of E-cadherin protein in vivo.
Multiple DGC cases in a family, DGC at a young age in an individual or the combination of DGC andlobular breast cancer (LBC) in an individual or a family define the hereditary DGC syndrome (HDGC), and testing for germline CDH1 mutations is warranted in HDGC.
Methylation-specific PCR analysis of seven genes frequently methylated in breast cancer (HIN-1, Twist, Cyclin D2, RARbeta, GSTP1, RASSF1A and CDH1) was performed on DNA from 67 Korean and 50 Caucasian invasive ductal breast cancers which were categorized into four subgroups by ER status and age.
In a case-control study, we also tested whether a variant adenine allele in the promoter polymorphism -161C-->A with a putative influence on the transcriptional activity of CDH1 in vitro confers any detectable risk of breast cancer.
These results suggested HNF3 may play important roles in the upregulation of the E-cadherin promoter, with the consequent re-expression of E-cadherin, thus reducing the metastatic potential of breast cancer cells.